This application, in response to RFA - MH - 09 - 021, proposes to investigate the feasibility and clinical utility of a computerized cognitive remediation program for adolescents with velo-cardio-facial syndrome (VCFS). VCFS, caused by a microdeletion on chromosome 22q11.2 and affecting 1:4000 individuals, is associated with specific neurocognitive deficits, behavioral disorders and, in up to 25% of older adolescents and young adults, schizophrenia. Two decades of research has firmly established that youth with VCFS exhibit deficits in attention, working memory and executive function. It is critical that we now design intervention programs that target these deficits, in order to improve the functioning of youth with this disorder and potentially, to moderate the onset of severe psychiatric symptomatology. In this application, we propose to adapt a previously validated, computerized, cognitive remediation program, focused on attention, executive function, and memory, for adolescents with VCFS, and to evaluate the clinical utility of the remediation program, utilizing standardized neuropsychological instruments, measures of adaptive functioning and virtual reality environments. Since relatively few youth with VCFS live within any given metropolitan area, we are proposing a highly innovative approach whereby our Syracuse-based cognitive coach will utilize high-speed internet connections and videoconferencing software to administer this remediation program to youth in their own homes. The R21 phase of the project will focus on a) adapting the remediation software for use with adolescents with VCFS, b) evaluating the tolerability and feasibility of administering the remediation software remotely, and c) developing / piloting virtual reality assessment software to include in our pre- and post-intervention assessments. The R33 phase of the project will evaluate the clinical utility of the cognitive remediation program. Using a crossover treatment design, we will bring 20 adolescents (ages 12 - 16 years) with VCFS to our medical center for four assessments: at baseline, 9 months, 18 months, and 24 months. The remote cognitive intervention itself will take place between the 9 and 18 month assessments. In order to ensure the ecological validity of our intervention, our assessments will consist of both standardized neuropsychological tests and assessments within the context of the virtual reality environments that we will develop during the R21 phase of the project. This project constitutes the initial steps toward implementing a far-reaching, effective intervention protocol that, potentially, will improve the daily lives of individuals with VCFS and foster a more independent trajectory to adulthood, thereby reducing the toll that this disorder takes on families and on society.